LEVERAXO

4). Posology The dosage depends on the intensity of pain and the patient’s individual susceptibility to the treatment.

The following general dosage recommendations apply:

Adults and adolescents (≥12 years) Dose titration In general, the initial dose for opioid naïve patients is 10 mg oxycodone hydrochloride given at intervals of 12 hours. Some patients may benefit from a starting dose of 5 mg to minimise the incidence of adverse reactions.

Patients already receiving opioids may start treatment with higher doses taking into account their experience with former opioid therapies. For doses not realisable/practicable with this medicinal product, other strengths and medicinal products are available.

According to well-controlled clinical studies 10-13 mg oxycodone hydrochloride correspond to approximately 20 mg morphine sulphate, both in the prolonged-release formulation. Because of individual differences in sensitivity for different opioids, it is recommended that patients should start conservatively with Leveraxo prolonged- release tablets after conversion from other opioids, with 50-75% of the calculated oxycodone dose.

Dose adjustment Some patients who take Leveraxo following a fixed schedule need rapid release analgesics as rescue medication in order to control breakthrough pain. Leveraxo prolonged-release tablets are not indicated for the treatment of acute pain and/or breakthrough pain.

The single dose of the rescue medication should amount to 1/6 of the equianalgesic daily dose of Leveraxo. Use of the rescue medication more than twice daily indicates that the dose of Leveraxo needs to be increased. The dose should not be adjusted more often than once every 1-2 days until a stable twice daily administration has been achieved.

Following a dose increase from 10 mg to 20 mg taken every 12 hours dose adjustments should be made in steps of approximately one third of the daily dose until the desired effect is achieved. The aim is a patient specific dosage which, with twice daily administration, allows for adequate analgesia with tolerable undesirable effects and as little rescue medication as possible as long as pain therapy is needed.

Even distribution (the same dose mornings and evenings) following a fixed schedule (every 12 hours) is appropriate for the majority of the patients. For some patients it may be advantageous to distribute the doses unevenly. In general, the lowest effective analgesic dose should be chosen.

For the treatment of non-malignant pain a daily dose of 40 mg is generally sufficient; but higher dosages may be necessary. Patients with cancer-related pain may require dosages of 80 to 120 mg, which in individual cases can be increased to up to 400 mg.

If even higher doses are required, the dose should be decided individually balancing efficacy with the tolerance and risk of undesirable effects. Elderly patients A dose adjustment is not usually necessary in elderly patients without clinically manifest impairment of hepatic or renal function.

Treatment goals and discontinuation Before initiating treatment with Leveraxo, a treatment strategy including treatment duration and treatment goals, and a plan for end of the treatment, should be agreed together with the patient, in accordance with pain management guidelines.

During treatment, there should be frequent contact between the physician and the patient to evaluate the need for continued treatment, consider discontinuation and to adjust dosages if needed. When a patient no longer requires therapy with oxycodone, it may be advisable to taper the dose gradually to prevent symptoms of withdrawal.

4). Duration of administration Oxycodone should not be used for longer than necessary. Patients with renal or hepatic impairment The dose initiation should follow a conservative approach in these patients. The recommended adult starting dose should be reduced by 50% (for example a total daily dose of 10 mg orally in opioid naïve patients), and each patient should be titrated to adequate pain control according to their clinical situation.

Other patients at risk Patients with low body weight or slow metabolisers, who are opioid naive should initially be treated with half the dose usually recommended for adults. e. 10 mg, may not be suitable as a starting dose and in such cases oxycodone hydrochloride 5 mg prolonged-release tablets can be used.

Paediatric population Children under 12 years of age Leveraxo should not be used in children under 12 years of age because of safety and efficacy concerns. Method of administration For oral use. Leveraxo should be taken twice daily based on a fixed schedule at the dosage determined.

The prolonged-release tablets may be taken with or independent of meals with a sufficient amount of liquid (½ glass of water). Leveraxo 5 mg prolonged-release tablets Leveraxo must be swallowed whole, and must not be divided, broken, chewed or crushed.

Leveraxo 10 mg prolonged-release tablets Leveraxo 20 mg prolonged-release tablets Leveraxo 30 mg prolonged-release tablets Leveraxo 40 mg prolonged-release tablets Leveraxo 60 mg prolonged-release tablets Leveraxo 80 mg prolonged-release tablets Leveraxo can be divided into equal doses.

However, do not chew or crush the tablet. Leveraxo should not be used with alcoholic beverages.

Summary of the safety profile Oxycodone can cause respiratory depression, miosis, bronchial spasms and spasms of the smooth muscles and can suppress the cough reflex. Tolerance and dependence may occur (see below). The most frequently reported undesirable effects are nausea (especially at the beginning of treatment) and constipation.

Respiratory depression is the chief hazard of an opioid overdose and occurs most commonly in elderly or debilitated patients. The adverse reactions considered at least possibly related to treatment are listed below by system organ class and absolute frequency.

Frequencies are defined as:

Very common (≥ 1/10) Common (≥ 1/100 to < 1/10) Uncommon (≥ 1/1,000 to < 1/100) Rare (≥ 1/10,000 to < 1/1,000) Very rare (< 1/10,000) Not known (cannot be estimated from the available data) Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Infections and infestations Rare: herpes simplex Immune system disorders Uncommon: hypersensitivity Very rare: anaphylactic reaction, anaphylactoid reaction Metabolism and nutrition disorders Common: decreased appetite or loss of appetite Uncommon: dehydration Rare: increased appetite Psychiatric disorders Common: anxiety (altered mood and personality change), confusional state, depression, decreased activity, restlessness, psychomotor hyperactivity, nervousness.

4). g. chest pain), malaise, oedema, peripheral oedema, drug tolerance, thirst Rare: weight increase, weight decrease Not known: drug withdrawal syndrome neonatal Injury, poisoning and procedural complications Uncommon: Injuries from accidents Description of selected adverse reactions Tolerance and dependence may develop with chronic use and a withdrawal syndrome may occur upon abrupt cessation of therapy.

The opioid abstinence or withdrawal syndrome is characterised by some or all of the following: restlessness, lacrimation, rhinorrhoea, yawning, perspiration, chills, myalgia, mydriasis and palpitations. Other symptoms also may develop, including: irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhoea, or increased blood pressure, respiratory rate or heart rate.

Drug dependence Repeated use of Leveraxo can lead to drug dependence, even at therapeutic doses. 4). Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard.

Caution must be exercised when administering oxycodone to the debilitated elderly, patients with severely impaired pulmonary function, patients with impaired hepatic or renal function, patients with myxoedema, hypothyroidism, Addison’s disease , toxic psychosis, prostate hypertrophy, alcoholism, known opioid dependence, delirium tremens, diseases of the biliary tract, pancreatitis, obstructive and inflammatory intestinal disease,, hypotension, hypovolaemia, head injury (due to risk of increased intracranial pressure), epilepsy or seizure tendency and in patients taking MAO inhibitors.

In suspicion or in case of paralytic ileus administration of Leveraxo has to be stopped immediately. Hepatobiliary disorders Oxycodone may cause dysfunction and spasm of the sphincter of Oddi, thus increasing the risk of biliary tract symptoms and pancreatitis.

Therefore, oxycodone has to be administered with caution in patients with pancreatitis and diseases of the biliary tract. Surgical procedures Leveraxo is not recommended for pre-operative use and must not be used for acute post-operative pain owing to the increased risk of persistent post-operative opioid use (PPOU) and opioid-induced ventilatory impairment (OIVI).

Respiratory- and cardiac depression The major risk of opioid excess is respiratory depression. It is most likely to occur in elderly or debilitated patients. Sleep-related breathing disorders Opioids can cause sleep-related breathing disorders including central sleep apnoea (CSA) and sleep-related hypoxemia.

Opioid use increases the risk of CSA in a dose- dependent fashion. In patients who present with CSA, consider decreasing the total opioid dosage. Risk from concomitant use of sedative medicines such as benzodiazepines or related drugs Concomitant use of Leveraxo and sedative medicines such as benzodiazepines or related drugs may result in sedation, respiratory depression, coma and death.

Because of these risks, concomitant prescribing with these sedative medicines should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe Leveraxo concomitantly with sedative medicines, the lowest effective dose should be used, and the duration of treatment should be as short as possible.

The patients should be followed closely for signs and symptoms of respiratory depression and sedation. 5). Drug dependence, tolerance and potential for abuse A comprehensive patient history should be taken to document concomitant medications, including over-the-counter medicines and medicines obtained on-line, and past and present medical and psychiatric conditions.

Tolerance Patients may find that treatment is less effective with chronic use and express a need to increase the dose to obtain the same level of pain control as initially experienced. Patients may also supplement their treatment with additional pain relievers.

These could be signs that the patient is developing tolerance. The risks of developing tolerance should be explained to the patient. Overuse or misuse may result in overdose and/or death. It is important that patients only use medicines that are prescribed for them at the dose they have been prescribed and do not give this medicine to anyone else.

Patients should be closely monitored for signs of misuse, abuse, or addiction. The clinical need for analgesic treatment should be reviewed regularly. Drug withdrawal syndrome Prior to starting treatment with any opioids, a discussion should be held with patients to put in place a withdrawal strategy for ending treatment with oxycodone.

Drug withdrawal syndrome may occur upon abrupt cessation of therapy or dose reduction. When a patient no longer requires therapy, it is advisable to taper the dose gradually to minimise symptoms of withdrawal. Tapering from a high dose may take weeks to months.

The opioid drug withdrawal syndrome is characterised by some or all of the following: restlessness, lacrimation, rhinorrhoea, yawning, perspiration, chills, myalgia, mydriasis and palpitations. Other symptoms may also develop including irritability, agitation, anxiety, hyperkinesia, tremor, weakness, insomnia, anorexia, abdominal cramps, nausea, vomiting, diarrhoea, increased blood pressure, increased respiratory rate or heart rate.

If women take this drug during pregnancy, there is a risk that their newborn infants will experience neonatal withdrawal syndrome. Hyperalgesia Hyperalgesia may be diagnosed if the patient on long-term opioid therapy presents with increased pain.

This might be qualitatively and anatomically distinct from pain related to disease progression or to breakthrough pain resulting from development of opioid tolerance. Pain associated with hyperalgesia tends to be more diffuse than the pre-existing pain and less defined in quality.

Symptoms of hyperalgesia may resolve with a reduction of opioid dose. Opioids, such as oxycodone hydrochloride, may influence the hypothalamic-pituitary- adrenal or – gonadal axes. Some changes that can be seen include an increase in serum prolactin and decreases in plasma cortisol and testosterone.

Clinical symptoms may manifest from these hormonal changes. Opioid Use Disorder (abuse and dependence) Tolerance and physical and/or psychological dependence may develop upon repeated administration of opioids such as oxycodone. Repeated use of Leveraxo may lead to Opioid Use Disorder (OUD).

A higher dose and longer duration of opioid treatment can increase the risk of developing OUD. Abuse or intentional misuse of Leveraxo may result in overdose and/or death. g. major […]

1 • Severe chronic obstructive lung disease • Cor pulmonale • Severe bronchial asthma • Severe respiratory depression with hypoxia • Elevated carbon dioxide levels in the blood (hypercarbia) • Paralytic ileus